There is an increasing interest in the development of arrays of surface-immobilized molecules for use as sensors, where molecular selectivity is achieved through a binding reaction with a sensor element often comprising a biological macromolecule (e.g., nucleic acid, protein, etc.). Thus, for example, strategies for the detection/quantification of nucleic acids can utilize arrays of DNA probes ready for hybridization. The nucleic acid to be analyzed is isolated and labeled with a fluorescent reporter group (Fidanza and McGall (1999) Nucleosides & Nucleotides, 18: 1293-1295; Lipshutz et al. (1999) Nature Genetics Chipping Forecast, 21: 20-24) and then hybridized to (incubated with) the array. The hybridization data are collected, e.g., as fluorescence emission from the label incorporated into the nucleic acid(s) hybridized to the probe array. Because the sequence and position of each probe on the array is known, the identity of the bound target nucleic acid is readily determined.
Similar approaches have been proposed that use microfabricated fiber optics to create high-density arrays of randomly ordered self-assembled bead-based sensors (Michael et al. (1998) Anal. Chem. 70: 1242-1248). Alternatively, semiconductor devices have been developed where small nucleic acids, or other capture probes, are electronically placed at, or “addressed” to, specific sites on a microchip. A sample is then analyzed for the presence of target molecules by determining which of the capture probes on the array bind to their cognate analyte in the sample (Edman et al. (1998) Nucl. Acids Res., 25: 4907-4914; Cheng et al. (1998) Nature Biotechnology, 16: 541-546).